A New Mouse Line for Identifying and Targeting Pericytes
Xingying Guo, Shangzhou Xia, Tenghuan Ge, Yangtao Lin, Shirley Hu et al.
(see article e0727242024)
Pericytes are essential for the integrity of the blood–brain barrier. However, because pericytes are broadly expressed in the body and have genetic overlap with other cell types, researchers have struggled to explore the distinct role of central nervous system (CNS) pericytes in health and disease. Guo and colleagues overcame this hurdle in mice by developing a genetic mouse line, which may serve as a tool for identifying and targeting CNS pericytes. They first used bioinformatics to identify the Atp13a5 gene as specific to CNS pericytes. Next, they created a knock-in mouse strain expressing cistronic tdTomato reporter and Cre recombinase in Atp13a5-expressing cells (CNS pericytes). This allowed them to investigate the timescale of Atp13a5-tdTomato expression and they discovered that it is detectable as early as embryonic day 15, when the blood–brain barrier becomes functional. Notably, expression increased during early postnatal development, suggesting that environmental cues may influence CNS pericyte specialization. This Atp13a5 mouse line may be a critical tool for improving our understanding of the role of pericytes in health and disease and will thus be of wide interest to neurovascular scientists.
Representative image of an embryonic cortex from a new genetic mouse line that enables visualization of central nervous system pericytes. See Guo et al. for more information.
Illuminating Mechanisms for Glutamate and GABA Co-release
Haram Kim, Soumil Dey, Gabriella Sekerková, and Marco Martina
(see article e0653242024)
It is established that glutamate and GABA can be co-released in the central nervous system, but how this occurs is unknown. In this issue, Kim and colleagues explored what underlies glutamate and GABA co-release in projections from the midbrain to dorsal hippocampus granule cells of mice. Using anterograde and retrograde viral tracing, optogenetics, immunostaining, in situ hybridization, and whole-cell patch-clamp recordings in acute brain slices, the authors discovered that glutamate and GABA co-release is driven by N- and P/Q-type calcium channels. They further found that μ-opioid receptors play a complex role in co-release of these neurotransmitters. Activation of μ-opioid receptors inhibited co-release via inhibition of presynaptic N-type calcium channels. However, μ-opioid receptor activation also increased co-release by inhibiting axo-axonic synapses from local interneurons. The discovery of this complex dual action by μ-opioid receptors is a major advancement in our understanding of co-release mechanisms in circuits that are strongly associated with reward and addiction.
Footnotes
This Week in The Journal was written by Paige McKeon
